AB0648 Cancer in systemic sclerosis: association between antibodies and malignancy and results from a third-level center
Authors: C. Sieiro Santos, C. Moriano, I. González Fernández, C. Álvarez Castro, A. López Robles, M. Martín Martín, E. Diez Alvarez
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) is associated with increased risk of malignancy. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. Some autoantibodies have been associated with a close temporal relationship with cancer. The absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer. Objectives To study the prevalence of cancer in SSc and the association between SSc-specific and SSc-associated autoantibodies and cancer in a third-level center. Methods We conducted a retrospective cohort study by including patients diagnosed with SSc followed from 1980 to 2020 fulfilling the 2013 ACR/EULAR SSc criteria. Demographic features, clinical and immunological characteristics were retrieved. The primary outcome was cancer-associated SSc, defined as cancer occurring within 2, 3 and 5 years of first non-Raynaud SSc manifestation. The exposure was defined by the presence of SSc-specific/associated autoantibodies, including anti-centromere (ACA), topoisomerase I (Scl70), RNA polymerase III, fibrillarin, Th/To, PM-Scl, Ku, TIF1g, Ro52. Descriptive analysis was used to compare clinical characteristics of subjects with cancer to those without cancer. Univariate logistic regression was used to compare the odds of cancer-associated SSc between the autoantibody subgroups. Results Out of 103 SSc subjects, 27 (26%) had a history of cancer following SSc diagnosis. Mean age was 61.9 (57-69) years, 70% were female and 88% had a smoking history. Median time between cancer and disease onset was 6.33 (3-9) years. Among patients with cancer, 12 (44%), 8 (29%) and 7 (26%) were diagnosed within 2, 5 and 10 years of SSc onset. The most frequent types were breast cancer (n=9), gastrointestinal cancer (n=5), prostatic cancer (n=4), hematological (n=3) cancers, cervical/uterine cancers (n=2), non-melanoma skin (n=2), lung cancer (n=2). Patients with cancer were more likely to be Sc70+(OR 2.55, 95% CI1.03-6.3, p 0.04), anti-TIF1g (OR 19.5, 95% CI 5.6 – 68.3, p 0.001) and RNA pol III (OR 10.9 CI 95% 1.08-109.3, p 0.04), have a history of smoking (OR 7.24, 95% CI 2.6-197, p 0.001), myositis (OR 5.2 IC 95% 2.06-13.2, p 0.005) and older age at SSc onset (61.9 vs 57, p 0.04). Breast cancer was more frequent in anti-TIF1g (OR 3.75 IC 95% 1.8-17.5) and RNA pol-III (OR 7.14 IC 95% 1.56-90.8) subgroups. The risk of cancer-associated SSc was significantly increased among anti-TIF1g-positive subjects at 5 years after SSc onset (OR 2.1 CI 95% (1.45-9.94), p 0.04) and among RNA-pol III-positive subjects at 2 years after SSc onset (OR 3.5 95% CI (1.2-51.4), p 0.02) (Table 1). Table 1. Logistic regression analysis for the risk of cancer within 2,5 and 10 years of SSc onset according to antibody positivity OR 95% CI for cancer diagnosis within 2 years of SSc onset OR 95% CI for cancer diagnosis within 5 years of SSc onset OR 95% CI for cancer diagnosis within 10 years of SSc onset Anti-Scl70 1.56 (0.51-44.5) 1.41 (0.27-12.7) 2.1 (0.55-13.4) Anti-centromere 1.72 (0.62-52.1) 1.52 (0.32-32.1) 1.69 (0.14-21.3) Anti-TIF1g 3.9 (0.35-43.4) 2.1 (1.45-9.94 ) 0.42 (0.04-5.32) ARN Pol III 3.5 (1.2-51.4 ) 1.9 (0.72-62.1) - Anti-PM Scl75/100 - - 0.87 (0.04-1.98) Anti-Ro52 2.5 (0.66-66.8) 2.0 (0.45-50.2) 0.63 (0.05-7.74) Conclusion Anti-Scl70, anti-TIF1g and RNA pol III were predictive of cancer-associated SSc for cancers. Breast cancer was the most frequent. Subjects with cancer were more likely to have a history of smoking, myositis and an older age at SSc onset. Autoantibodies should be taken into account in cancer screening. Larger studies are needed to define the risk of cancer-associated SSc in different autoantibody subgroups. References [1]Mecoli CA, Adler BL, Yang Q, Hummers LK, Rosen A. Cancer in Systemic Sclerosis: Analysis of Antibodies Against Components of the Th/To Complex. Arthritis Rheumatol. 2021 Feb;73(2):315-323. doi: 10.1002/art.41493. Epub 2020 Dec 26. PMID: 33241644; PMCID: PMC7884482 Disclosure of Interests None declared